The present invention relates to a hardenable multi-part liquid acrylic composition comprising a radiopacifying filler, in particular but not exclusively, an acrylic composition which has at least two liquid parts which react with each other upon being mixed together to form a cement such as a bone cement which hardens to a solid, an at least twin barreled syringe or caulking gun accommodating the multi-part composition and a method of producing the multi-part composition.
Hardenable compositions formed by mixing together acrylic polymers and monomers are useful in a wide range of applications. Particular utility is found in dental, medical, adhesive and construction applications, where such materials have been used for over 40 years.
Dental applications include denture bases, denture base plates, denture liners, denture repairs, custom trays, veneering for crowns and bridgework, artificial teeth, veneers and repair for natural teeth and tooth restorative fillings. Medical applications include bone cements for bone cavities such as prosthetic cements, cranial cements and vertebral cements in vertebroplasty and kyphoplasty. Further applications include the production of shaped articles that harden extra-corporeally and which can then be introduced into the body.
Hardenable acrylic compositions are generally composed of a solid component and a liquid component. The solid component comprises a powder formed from polymer particles and, if appropriate, further additives, such as polymerization initiators and catalysts, fillers, pigments and dyestuffs. The liquid component comprises a liquid monomer or monomers and further additives, such as accelerators and stabilisers. When ready for use, the solid and liquid components are mixed together to form a liquid or semi-solid paste, which, under the action of the polymerization initiators and accelerators, increases in viscosity and hardens into a solid.
However, research has also been undertaken in relation to liquid first and second parts. Such two part compositions may permit easier mixing of the two parts. WO98/24398 (Lautenschlager et al) describes a bone cement system of low porosity prepared by mixing together two liquid components. Each liquid component consists of solutions of PMMA in MMA monomer, with one solution containing an initiator (e.g., BPO) and the other solution containing an activator (e.g. DMPT). This system has the disadvantages of limited storage stability, a relatively high polymerization exotherm and an increased shrinkage that is produced by the necessarily higher levels of MMA that are required to prepare the solutions. WO2010/005442 (Hasenwinkel et al) attempts to overcome some of these disadvantages by incorporating cross-linked PMMA beads into the solutions. However, the disadvantage of limited storage stability remains.
US2011/0054392 and EP 2,139,530 (Nies) describe an implant material for improved release of active ingredients comprising two components. The first component comprises a mixture of polymer powder and BPO initiator that is made into a stable non-settling paste by adding water, surface active agent (e.g. Tween 80) and a water soluble polymer (e.g., carboxymethyl starch). The second component comprises a solution of PMMA dissolved in MMA monomer plus DMPT accelerator. Each component is charged to separate compartments of a double chamber syringe and mixed by pressing through a static mixer. The high water content provides high porosity in the final hardened product facilitating the improved release of active ingredients. However, the relatively high porosity (typically approximately 16% and higher) creates the disadvantage of reduced mechanical properties in the final cement, such as a reduced compression strength that is less than acceptable for conventional bone cements.
Additional prior art documents De Wijn, J. Biomed. Mater. Res. Symposium, No 7, pp 625-635 (1976), U.S. Pat. No. 4,093,576, Boger et al., J. Biomed. Mat. Res. Part B: Applied Biomaterials, volume 86B, part 2, pp 474-482 (2008) and WO2004/071543 discuss the inclusion of water in a bone cement system, but not for the purpose of delivery via a double chamber syringe and mixing by pressing through a static mixer.
De Wijn in J. Biomed. Mater. Res. Symposium, No 7, pp 625-635 (1976) and in U.S. Pat. No. 4,093,576 describes mixing of a conventional polymer powder with a gelling agent in powder form, e.g. carboxymethylcellulose (CMC). Monomer is then added to form a cement dough, followed by the addition of water to produce gelling with the CMC. The resultant mixture is then cured to form a porous material. The open pore structure of the porous material is said to allow for tissue invasion over time to further anchor the implant with surrounding connective tissue or bone. However, the porous nature of the material again creates the disadvantage of reduced mechanical properties compared to conventional bone cements.
Boger et al in J. Biomed. Mat. Res. Part B: Applied Biomaterials, volume 86B, part 2, pp 474-482 (2008) and Bisig et al in WO2004/071543 describe an injectable low modulus PMMA bone cement for osteoporotic bone. This system consists of three components, namely the powder and liquid components of a conventional two-component bone cement, plus an aqueous solution of hyaluronic acid. Porous materials result that are claimed to have mechanical properties close to that of human cancellous bone, significantly lower than the mechanical properties of conventional bone cement.
Radiopacifying fillers such as barium sulphate may traditionally be added to a solid-liquid bone cement composition in either the first or second part, or both. However, the introduction of filler particles has a tendency to also reduce the mechanical properties of the hardened composition such as flexural, tensile and fatigue properties. Accordingly, introducing radiopacifying filler into liquid—liquid two part compositions also presents significant mechanical property issues.
A further problem arises when mixing a liquid first part and a liquid second part such as through a static mixer connected to twin compartments of a syringe or caulking gun if the viscosity of one or both of the liquids is too high or the viscosity of the liquids are significantly different to each other.
One solution to the problem is to reduce the viscosity of a higher polymer content liquid part and match it more closely to the viscosity of the lower polymer or monomer containing liquid part.
The viscosity could be reduced by increasing the amount of liquid carrier (e.g. water) in the liquid part. However, higher levels of water in the reacted two part acrylic composition increase the amount of porosity and therefore also reduce the mechanical properties in the final bone cement. Radiopacifying fillers tend to increase viscosity still further exacerbating this viscosity problem when they are used.
U.S. Pat. No. 4,500,658 discloses that a problem with certain types of metal filler such as lead foil, silver alloy, gold and 1% set amalgam are that they cause stress concentrations at the interface between the insert and the resin which weakens and fractures the material.
On the other hand, heavy metal compounds externally attached to the beads are inconvenient. In addition, it is pointed out that high levels of barium sulphate are necessary in the resin to render it radiopaque but that at these levels there is a negative impact on the strength of the material. The document describes that the filler can be encapsulated and uniformly dispersed in the bead using suspension polymerisation. The beads are said to be useful in biomedical applications to colour biomedical materials and devices. An example is proposed of compounding the bead particles into a dry powder for a solid-liquid denture composition. The beads may be ground up prior to use in a composition. The mixtures with monomer disclosed imply that most of the bead is dissolved in the monomer thereby allowing encapsulated radioopaque pigment to disperse in the monomer. Accordingly, the document merely teaches a manner of opacifer delivery to the matrix of the final polymer. However, no mention is made of using the bead particles in a liquid-liquid system or any advantages in so doing. EP0218471 teaches that barium sulphate radiopacifier incorporated into ethylmethacrylate beads can give improved mechanical properties with n-butyl methacrylate monomer in a solid liquid system. There is no mention of the possibility to reduce the concentration of radiopacifying filler particles through encapsulating within acrylic polymer bead particles, nor do they mention any effect on viscosity of a liquid-liquid bone cement system as it is only used as the component of a bone cement powder. Furthermore, upon mixing the bead polymer is said to be almost fully dissolved in monomer so that there is no intention to maintain encapsulation in the final product.